Hemolytic events associated with intravenous immune globulin therapy: a qualitative analysis of 263 cases reported to four manufacturers between 2003 and 2012

Transfusion. 2015 Jul:55 Suppl 2:S36-46. doi: 10.1111/trf.13198.

Abstract

Background: Objectives of this study were to identify possible patient and product risk factors for intravenous immune globulin (IVIG)-associated hemolysis, a recognized side effect of IG therapy; analyze IVIG indications; and examine dose levels (g/kg body weight) and total IVIG dose administered.

Study design and methods: Reports of IVIG-associated hemolysis for 10 years (2003-2012) for four participating IG manufacturers were identified using a uniform case definition (Standardized MedDRA Query "Hemolytic disorders," Broad Scope, Version 16.0) and analyzed.

Results: IVIG-associated hemolysis appears to occur predominantly at dose levels exceeding 0.5 g/kg, with 72% of cases with known dose information having dose levels between 1 and 2.5, and can affect patients at any age, without a clear gender preference. No association was found between hemagglutinin exposure and development of hemolysis, nor between dose levels and odds of receiving a transfusion to treat hemolysis. Patients with blood group AB may be at higher risk of hemolysis than those with group A or B.

Conclusion: Data examined confirm that IVIG-associated hemolysis predominantly occurs following infusion of high IVIG doses, and can affect patients at every age of both genders. While presence of hemagglutinins appears to play a major role in pathogenesis of hemolytic disorders, high hemagglutinin titers of IVIG products themselves seem to be of less relevance, indicating that the pathomechanism of IVIG-associated hemolysis may be related to the presence, but not the absolute amount, of hemagglutinins. Patients with hemolysis had additional hemolytic risks such as multiple comorbidities and medication use. IG-treated patients with multiple risks should be closely monitored for hemolysis.

MeSH terms

  • ABO Blood-Group System / blood
  • Female
  • Hemagglutinins / administration & dosage
  • Hemagglutinins / adverse effects*
  • Hemolysis / drug effects*
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage
  • Immunoglobulins, Intravenous / adverse effects*
  • Male
  • Retrospective Studies
  • Risk Factors
  • Sex Factors

Substances

  • ABO Blood-Group System
  • Hemagglutinins
  • Immunoglobulins, Intravenous